Intranasal Red Light Probe For Treating Alzheimer&#39;s Disease

ABSTRACT

A method of treating Alzheimer&#39;s Disease in which intranasal red light devices are used to shine red light upon the brain structures.

CONTINUING DATA

This divisional patent application claims priority from co-pending U.S.Ser. No. 11/154,754, filed Jun. 16, 2005, entitled “Intransal Red LightProbe for Treating Alzheimer's Disease” (DiMauro).

BACKGROUND OF THE INVENTION

In Alzheimer's Disease (AD), the cleavage of beta amyloid proteinprecursor from the intracellular membrane often produces a protein AB-42which is incompletely removed by normal clearance processes. Over time,this protein is deposited as a beta amyloid protein (Aβ) plaque withinbrain tissue, leading to the local destruction of neurons. The Aβ plaquedeposition is also believed to provoke an inflammatory response bymicroglia and macrophages. These cells are believed to respond to theplaque deposition by releasing pro-inflammatory cytokines and reactiveoxygen species (ROS). Although the inflammatory response may be provokedin an effort to clear the brain tissue of the detrimental plaque, it isnow believed that this inflammation also injures local neuronal tissue,thereby exacerbating AD.

Now referring to FIG. 1, in most AD cases, the progression of AD beginsin the hippocampus, wherein the patient suffers a loss of short termmemory. From the hippocampus, the disease spreads to the amydgala, andthen proceeds anteriorly to the prefrontal cortex. Since the prefrontalcortex controls problem-solving, a person suffering from AD begins tolose their ability to learn when the disease affects the prefrontalcortex. In general, impairment of the prefrontal cortex begins to appeara few years after loss of short-term memory.

The olfactory bulb (OB) is located just above the top of the nasalcavity and is intimately involved in the sense of smell. Olfactory nervefibers located in the nasal cavity extend through the cribriform plateand enter the OB along its longitudinal axis. The OB projects throughthe lateral olfactory tracts to the olfactory tubercles, the pyriformcortex, the cortical amygdala nucleus and the ventrolateral entorhinalarea.

There is substantial evidence that the OB is one of the first portionsof the brain affected by AD. Davies, Neurobiol. Aging, 1993, July-Aug.14(4) 353-7. Investigators have found significant early tau-relatedpathology in the OB of AD patients. Tsuboi, Neurpathol. Appl. Neurobiol.2003, Oct. 29(5) 503-10. Increased numbers of neuritic plaques andneurofibrillary tangles on the OB have been demonstrated in AD patients.Yamamoto, Yakunutsu Seishin Kodo, Aug. 11(4), 223-35.

In addition to its olfactory functions, the OB is particularly rich inacetylcholine and other neurotransmitters and delivers theseneurotransmitters to other portions of the brain. Since the OB is wellinterconnected within the brain, destruction of the OB by AD may welllead to accelerated destruction of other portions of the AD brain. Someinvestigators have suggested that neural injury to the OB may result incollateral damage to other limbs of the cholinergic system. For example,it has been found that lesioning of the OB results in severely reducedexpression of BDNF expression in an afferent structure, the hlDBB, andreduced choline uptake and ChAT activity locally and in the cingulatedcortex. Sohrabji, J. Neurobiol., 2000, Nov. 5, 45(2) 61-74. Someinvestigators have found that the most severely affected areas of the ADbrain are interconnected with the central olfactory system in contrastto the relative sparing of the other sensory areas which lack olfactoryconnection. Kovacs, Neurpathol. Appl. Neurobiol., 1999, Dec. 25(6)481-91.

Indeed, many investigators have reported that olfactory bulbectomy leadsto severe impairment in memory or learning. Yamamoto, Yakunutsu SeishinKodo, Aug. 11(4), 223-35; Yamamoto, Behav. Brain. Res. 1997, Feb.83(1-2) 57-62; Hozumi, Behav. Brain Res. 2003, Jan. 6, 138(1) 9-15; andHallam, Behav. Brain Res. 2004, Aug. 31, 153(2):481-6. Hallam, supra,and Hozumi, supra, have tied this collateral deficit to impairment ofthe cholinergic system. Other investigators have suggested thatbulbectomy initiates in the brain a pathological process similar tohuman Alzheimer's Disease in location, biochemistry and behaviouralmanifestations. Aleksandrova, Biochemistry (Mosc), 2004, Feb. 69(2)176-180.

A minority of investigators have even proposed that AD may begin in theOB due to pathogens entering via peripheral olfactory apparatus. Mann,Mech. Ageing Dev., 1988, Jan. 42(1) 1-15. It has also been reported thatneurofibrillary tangles spread from the entorhinal cortex to the limbicsystem, then to cortical areas, according to Braak's stages. Kovacs,Neuroreport. 2001, Feb. 12, 12(2) 285-8. However, these hypotheses havebeen disputed. See Davies, supra and Kovacs, Neuroreport. 2001, Feb. 12,12(2) 285-8.

In sum, because the olfactory bulb plays a keep role in the cholinergicsystem in the cerebral cortex, damage to the olfactory bulb not onlyimpairs the patient's sense of smell, it also impairs vital systemsrelated to learning and memory due to disruption of the cholinergicsystems.

Because of the role played in AD by inflammation, anti-inflammatorycompounds have been identified as candidates for treating Alzheimer'sDisease. However, the delivery of these compounds has generally beenthrough an oral route, and the systemic side effects associated withlong term use of these compounds are often undesirable.

Some investigators have proposed implanting an effective amount of NGFin a sustained release device for treating Alzheimer's Disease. However,NGF simply helps restore damaged neurons—it does little to stop thedamage from occurring.

Other have examined the possibility of intranasal installation oftherapeutic peptides in the form of drops. However, it is not knownwhether significant amounts of these peptides are able to cross throughthe nasal mucosa and into the cerebral cortex.

SUMMARY OF THE INVENTION

The present invention is based upon the realization that the cribriformplate portion of the nasal cavity is substantially permeable to redlight. Because of that permeability, therapeutic doses of red light maybe non-invasively administered from the nasal cavity through thecribriform plate and through the OB of the prefrontal cortex of thebrain. The resultant irradiation of the OB with red light is expected tohave many beneficial effects upon a person suffering from AD.

It has been reported in the literature that near infra-red light savesneurons that have been challenged by neurotoxics from apoptosis. Inparticular, Wong-Riley, J. Biol. Chem. 2004, e-pub Nov. 22, reports thatirradiating neurons with 670 nm red light significantly reduced neuronalcell death induced by 300 mM KCN from 83.6% to 43.5%.

The general concept of repairing brain cells through red lightirradiation is also well supported by the literature. Wollman, Neurol.Res. 1998, July 20(5) 470-2 reports that providing daily 3.6 J/cm² dosesof red light from a He—Ne laser to cortex explants resulting in caused asignificant amount of sprouting of cellular processes outgrowth. Wollmanconcludes that the irradiation induces neurite processes sprouting andimproves nerve tissue recovery. Similarly, Wollman, Neurol. Res. 1996Oct. 18(5) 467-70 reports the enhanced migration and massive neuritesprouting of cultured rat embryonal brain cells subject to an 8 minutedose of a 0.3 mW, He—Ne laser. Therefore, the red light of the presentinvention may further cause repair and regeneration of damaged neuronalcells.

Therefore, it is expected that transmitting an effective amount of redlight across the cribriform plate to the olfactory bulb will have bothneuroprotective and neuroregenerative effects upon the olfactory bulb.The therapeutic benefits provided to the OB are expected to extend toits afferents, including enhanced BDNF supply and improved cholinergictransmission. Accordingly, learning and memory may be improved, or theirdeficits delayed.

Therefore, in accordance with the present invention, there is provided amethod of treating a patient having an olfactory bulb, comprising:

a) irradiating the olfactory bulb with an effective amount of red light.

Also in accordance with the present invention, there is provided amethod of treating or preventing Alzheimer's disease, comprising thesteps of:

a) providing an implant having a red light source,

b) positioning the implant within a nasal cavity, and

c) activating the red light source to irradiate brain tissue with anamount of red light.

DESCRIPTION OF THE FIGURES

FIG. 1 discloses a saggital cross section of a brain afflicated withAlzheimer's Disease.

FIG. 2 discloses a cross-sectional side view of the nasal cavity,wherein the cribriform plate is a wafer-thin ledge of porous bonytissue.

FIG. 3 discloses a coronal view of the cribriform plate.

FIG. 4, this frontal cross-section of the skull.

FIGS. 5 a-5 c disclose side, front and upper views of a red lightemitting intranasal device of the present invention.

FIG. 6 is a medial cross-section of the cerebrum showing the adjacencyof the sphenoidal sinus and the hypothalamus.

FIG. 7 shows a catheter of the present invention inserted into thesphenoidal sinus and irradiating the hypothalamus.

FIG. 8 shows a catheter of the present invention inserted into thesphenoidal sinus and diffusing light in a plurality of direction.

FIG. 9 shows a catheter of the present invention inserted into thesphenoidal sinus and having an inflated balloon.

FIG. 10 shows a light transmissive pin of the present invention insertedinto bone adjacent the sphenoidal sinus and oriented towards thehypothalamus.

FIG. 11 shows a horizontal section of the head showing the adjacency ofthe sphenoidal sinus and the medial surface of the temporal lobe.

FIG. 12 shows a cross-section in which a light-transmissive pin of thepresent invention inserted into the bone in the roof of the mouth.

FIG. 13 a&b represent cross-sections of an implant of the presentinvention implanted within the sphenoidal sinus.

FIG. 14 represents a cross-section of an implant of the presentinvention having a red light LED and implanted within the sphenoidalsinus.

FIG. 15 represents a cross-section of an implant of the presentinvention having a red light LED and an Rf antenna.

DETAILED DESCRIPTION OF THE INVENTION

Now referring to FIG. 1, there is provided a saggital cross section of abrain afflicated with Alzheimer's Disease. In general, the diseasebegins in the hippocampus, spreads to the amydgala, and proceedsanteriorly to the prefrontal cortex.

Now referring to FIG. 2, the cribriform plate CP is a wafer-thin ledgeof porous bony tissue located beneath the prefrontal cortex portion ofthe brain and above the nasal cavity. The porosity of the cribriformplate is filled with olfactory nerves extending from the olfactory bulbOB (located at the lower base of the brain) and terminating within thenasal mucosa. As shown here, the cribriform plate has a thickness ofabout 1 mm while the olfactory bulb has a thickness of about 3 mm. Thus,red light will traverse 1 mm of nerve fiber tissue within the cribriformplate and 3 mm of grey matter associated with the olfactory bulb,totaling to about 4 mm.

Now referring to FIG. 3, the coronal view of the cribriform plate CPreveals that fairly large throughholes extend transversely through aboutone-half of the cribriform plate. These throughholes comprises about 50areal % of the cribriform plate.

Now referring to FIG. 4, this frontal cross-section shows that thethickness cribriform plate and the olfactory bulb comprise only abouttwo mm.

Therefore, since about one half of the face of the cribriform platecomprises porosity filled with light-permeable nervous tissue, red lightshined through the cribriform plate from the nasal cavity will encounteronly soft, light permeable nervous tissue about half of the time.Because red light is about to penetrate gray matter to a depth of up toa centimeter, portions of the prefrontal cortex as deep as about onecentimeter can be irradiated with red light. In instances wherein thecombined thickness of the cribriform plate and olfactory bulb are lessthan about 1 cm, portions of the prefrontal cortex may also betherapeutically irradiated.

Moreover, since red light experiences high diffraction as it proceedsthrough soft tissue, it is possible for the entire lower portion of theprefrontal cortex to be irradiated with red light.

Therefore, in accordance with the present invention, there is provided amethod of treating or preventing Alzheimer's disease, comprising thesteps of:

-   -   a) providing an device having a fiber optic and a red light        source,    -   b) positioning the fiber optic within a nasal cavity, and    -   c) activating the red light source to irradiate brain tissue        with an effective amount of red light.

Without wishing to be tied to a theory, it is believed that thetherapeutic neuroprotective and neuroregenerative effects of red lightdescribed above may be due to a) an increase in ATP production in theirradiated neurons, and b) an increase in the activity of localanti-oxidant enzymes superoxide dismutase (SOD) and catalase.

It is believed that irradiating neurons in the brain with red light willlikely increase ATP production from those neurons. Mochizuki-Oda,Neurosci. Lett. 323 (2002) 208-210, examined the effect of red light onenergy metabolism of the rat brain and found that irradiating neuronswith 4.8 W/cm² of 830 nm red light increased ATP production in thoseneurons by about 19%.

Without wishing to be tied to a theory, it is further believed that theirradiation-induced increase in ATP production in neuronal cell may bedue to an upregulation of cytochrome oxidase activity in those cells.Cytochrome oxidase (also known as complex IV) is a major photoacceptorin the human brain. According to Wong-Riley, Neuroreport, 12:3033-3037,2001, in vivo, light close to and in the near-infrared range isprimarily absorbed by only two compounds in the mammalian brain,cytochrome oxidase and hemoglobin. Cytochrome oxidase is an importantenergy-generating enzyme critical for the proper functioning of neurons.The level of energy metabolism in neurons is closely coupled to theirfunctional ability, and cytochrome oxidase has proven to be a sensitiveand reliable marker of neuronal activity.

Importantly, the literature has made a direct association betweendefects in cytochrome c oxidase and Alzheimer's Disease. See, e.g.,Cottrell, Neuropathol. Appl. Neurobiol. 2002, Oct. 28(5) 3906; Cottrell,Neurology, July 24, 57(2) 260-4. Alieu, Neurol. Res., 2003, September.25(6) 665-74. Aliev, Ann NY Acad. Sci., 2002, Nov. 977, 45-64.

By increasing the energetic activity of cytochrome oxidase, the energylevel associated with neuronal metabolism may be beneficially increased.Indeed, the literature reports that red light reverses the inhibitoryeffects of neurotoxins upon cytochrome oxidase activity, leading toincreased energy metabolism in neurons functionally inactivated bytoxins. Wong-Riley Neuroreport 12(14) 2001:3033-3037 and Wong-Riley, J.Biol. Chem., e-pub, Nov. 22, 2004.

According to Kamanli, Cell Biochem. Func. 2004, 22:53-57, catalasedetoxifies hydrogen peroxide and converts lipid hydroperoxides intonon-toxic alcohols, and is essential for the inhibition of inflammationrelated to the function of neutrophils.

Romm, Biull. Eksp. Biol. Med. 1986 Oct. 102(10) 426-8 reports that laserirradiation of wounds results in a decreased chemiluminescence that isattributable to activation of catalase in the tissue fluid.

Therefore, it is believed that irradiating the AD brain with aneffective amount of red light will therapeutically increase of theactivity of catalase in the irradiated region, thereby attenuating thedeleterious effect of hydrogen peroxide upon the neurons in the ADbrain.

According to Kamanli, supra, SOD catalyses dismutation of the superoxideanion into hydrogen peroxide.

The literature repeatedly reports that red light irradiation ofinactivated SOD increases its activity. For example, Vladimirov,Biochemistry (Moscow) 69(1) 2004, 81-90 provides a review including thephotoreactivation of Cu—Zn SOD under He—Ne laser. Karu, Laser Ther.1993, 5, 103-9 reports that reactive oxygen species in human blood werefound to be suppressed after laser diode illumination at 660 nm, 820 nm,880 nm and 950 nm. This affect has been attributed by other authors tothe activation of SOD or catalase. Volotovskaia Vopr Kurortol ZizioterLech Fiz Kult 2003 May-June(3)22-5 reports that 632 nm He—Ne laserirradiation of blood has an anti-oxidant effect as shown by activationof SOD. Ostrakhovich Vestn Ross Akad Med Nauk. 2001(5) 23-7 reports thatinfrared pulse laser therapy of RA patients caused an increase in SODactivity. Gorbatenkova Biofizika, 1988 July-August 33(4) 717-9 reportsthat SOD that was inactivated by hydrogen peroxide was reactivated by a450-680 nm red light laser. Vladimirov, Free Rad. Biol. Med. 1988,5(5-6) 281-6 reports the inactivation of SOD by its incubation in a lowpH 5.9 solution and its subsequent reactivation by helium-neon laserlight. Catalase was found to be reactivated as well. Cho, In Vivo, 2004,September.-October 18(5) 585-91 reports on the use of low level lasertherapy (LLLT) to treat knee joints that have been induced with OA byinjection of hydrogen peroxide. SOD was reported to increase about 40%in the OA group as compared to controls.

Therefore, it is believed that irradiating the AD brain with aneffective amount of red light will therapeutically increase of theactivity of SOD in the irradiated region, thereby attenuating thedeleterious effect of superoxide anion upon the neurons in the AD brain.

According to Leung, Laser Surg. Med. 31:283-288 (2002), nitric oxideenhances oxidative insult by reacting with superoxide anion to form astronger oxidant, peroxynitrite, which leads to mitochondrialdysfunction, DNA damage and apoptosis. Haas, Neuroscience Letters, 322,(2002) 121-126 reports that iNOS is induced by amyloid plaques in ADbrains, and is responsible for producing NO, which is considered to behighly neurotoxic when generated in excess.

Leung, supra, investigated the effect of low energy red laser afterstroke in rats, and found that red light can suppress NO synthaseactivity. In particular, Leung found that irradiating a portion of therat's brain with a 660 nm red light (average power 8.8 mW, 2.64 J/cm²)reduced NOS activity up to about 80% over that in unirradiated strokerats, and up to about 60% over the NOS activity in normal rats. Leungconcluded that the main findings of the study was that low energy lasermay be protective by suppressing the activity of NOS in cerebralischemia and reperfusion.

Without wishing to be theory, it is believed that irradiation of aportion of an Alzheimer's brain will similarly therapeutically suppressNO synthase activity, thereby attenuating peroxynitrite activity.

It is noted that Leung, supra, also reported that red light irradiationof the brain resulted in a TGF-β tissue concentration of 1-6 ng/ugprotein of tissue. Thus, red light irradiation of the OB may very wellbe an attractive non-invasive way of generating large amounts of TGF-βwithin the brain.

Moreover, the literature has reported other highly beneficial effects ofred light, including its attenuation of the immune response followingneuronal injury. Byrnes, Lasers Surg. Medicine 9999:1-15 (2005) reportsthat 810 nm light promotes the regeneration and functional recovery ofthe injured spinal cord, and significantly suppressed IL-6 and iNOSexpression and immune cell activation. Of note, Byrnes reports a171-fold decrease in IL-6 expression and an 80% reduction in iNOSexpression when the spinal cord lesion was irradiated on a daily basiswith about 100 J/cm² red light for about 2 weeks.

The ability of red light to suppress IL-6 in injured neuronal matter isimportant to the present invention because IL-6 is thought to play amajor role in AD pathology. For example, Del Bo, Neuroscience Letters188 (1995) 70-74 reports that IL-6 increased mRNA levels of beta-amyloidprecursor protein (APP) in a dose dependent relationship. Qiu, J.Neuroimmunology, 139, (2003) 51-57 reports that IL-6 is thought tocontribute to AD by increasing amyloidogenesis. Huell, Acta Neuropathol.(Berl) 1995; 89(6) 544-51 reports that IL-6 is found in early stages ofplaque formation and is restricted to the brain of AD patients. In sum,it appears that IL-6 plays and early role in the pathology of AD.Therefore, reducing the IL-6 expression in and around AD lesions may bequite helpful.

Also without wishing to be tied to a theory, it is further believed thatred light may also be effective in causing the release of calcitoningene related peptide (CGRP), which in turn may cause mast cells todegranulate and release IL-10, thereby attenuating AD.

Preferably, the red light of the present invention has a wavelength ofbetween about 650 nm and about 1000 nm. In some embodiments, thewavelength of light is between 800 and 900 nm, more preferably between800 nm and 835 nm. In this range, red light has not only a largepenetration depth (thereby facilitating its transfer to the fiber opticand SN), but Wong-Riley reports that cytochrome oxidase activity issignificantly increased at 830 nm, and Mochizuki-Oda reported increasedATP production via a 830 nm laser.

In some embodiments, the wavelength of light is between 600 and 700 nm.In this range, Wong-Riley reports that cytochrome oxidase activity wassignificantly increased at 670 nm. Wollman reports neuroregenerativeeffects with a 632 nm He—Ne laser.

Respecting penetration depths, Byrnes, Lasers Surg. Medicine 9999:1-15(2005) reports that an effective amount of 810 nm light was able totraverse a 1 cm thick rat spinal cord. The penetration depths of variouswavelengths of red light in grey matter brain tissue have been reportedin Yaroslavsky, Phys. Med. Biol. 47 (2002) 2059-73 as follows:

Wavelength Penetration Depth (mm) 630 nm 0.83-4.06 675 nm 1.29 670 nm4.4 1064 nm 1.18-3.28

In some embodiments, the light source is situated to irradiate adjacenttissue with between about 0.02 J/cm² and 200 J/cm² energy. Withoutwishing to be tied to a theory, it is believed that light transmissionin this energy range will be sufficient to increase the activity of thecytochrome oxidase and anti-oxidant activity around and in the OB. Insome embodiments, the light source is situated to irradiate targettissue with more than 10 J/cm², and preferably about 100 J/cm² energy.In some embodiments, the light source is situated to irradiate adjacenttissue with between about 0.2 J/cm² and 50 J/cm² energy, more preferablybetween about 1 J/cm² and 10 J/cm² energy.

In some embodiments, the light source is situated to produce an energyintensity of between 0.1 watts/cm² and 10 watts/cm². In someembodiments, the light source is situated to produce about 1milliwatt/cm².

Of note, it has been reported that the neuroprotective effects of redlight can be effected by a single irradiation on the order of minutes.Wong-Riley, J. Biol. Chem. 2004, e-pub Nov. 22, reports that irradiatingneurons with 670 nm red light for only ten minutes results inneuroprotection. Similarly, Wong-Riley Neuroreport 12(14) 2001:3033-3037reports that a mere 80 second dose of red light irradiation of neuronprovided sustained levels of cytochrome oxidase activity in thoseneurons over a 24 hour period. Wong-Riley hypothesizes that thisphenomenon occurs because “a cascade of events must have been initiatedby the high initial absorption of light by the enzyme”.

Therefore, in some embodiments of the present invention, the therapeuticdose of red light is provided on approximately a daily basis, preferablyno more than 3 times a day, more preferably no more than twice a day,more preferably once a day.

In some embodiments, the red light irradiation is delivered in acontinuous manner. In others, the red light irradiation is pulsed inorder to reduce the heat associated with the irradiation. Withoutwishing to be tied to a theory, it is believed that pulsed light may bemore effective in achieving the vibratory oscillation of the catalaseand SOD molecules.

In some embodiments, red light is combined with polychrome visible orwhite light.

Now referring to FIGS. 5 a-5 c, there is provided a probe 1 for treatinga neurodegenerative disease in a patient, comprising:

-   -   a) a distal portion 3 adapted to fit within an upper portion of        a nasal cavity and having a red light emitter 5 oriented towards        the cribriform plate,    -   b) a flexible intermediate portion 7 having an angled, narrowed        portion 9,    -   c) a proximal portion 11 having a handgrip 13 having a knurled        surface 15 and a red light activation button 17,    -   d) a red light source (not shown),    -   e) a fiber optic cable (not shown) connecting the red light        source and the red light emitter.

In some embodiments, the height of the distal portion is greater thanits width. This allows orientation. In some embodiments, the distalportion is detachable from the remainder of the device. This allows itto be periodically cleaned by the user. In some embodiments, the tip ofthe distal portion is rounded in order to ease the entry of the distalportion in the nasal passage. In some embodiments, the length of thedistal portion corresponds substantially to the length of the cribriformplate. This allows the red light emitter to emit light alongsubstantially the entire porosity of the cribriform plate. In someembodiments, the length of the red light emitter correspondssubstantially to the length of the cribriform plate. In someembodiments, the red light emitter is oriented to face the cribriformplate upon insertion in the nasal passage. In some embodiments, thedistal portion has an upper surface oriented to face the cribriformplate upon insertion. In some embodiments, the red light emitter emitslight in an arc of less than 180 degrees. In some embodiments, the redlight emitter emits light substantially lateral to the longitudinal axisof the proximal portion.

In some embodiments, the narrowed portion is provided along only oneaxis, thereby providing preferred bending.

In some embodiments, the red light source is located in the proximalportion. In some embodiments, the red light source is located in thedistal portion. In some embodiments, the red light source is operated bya battery contained within the device. In some embodiments, the redlight source is operated by an electric power cord connected to thedevice.

In some embodiments, a light reflective surface is provided around thered light emitter to concentrate the light.

Therefore, in accordance with the present invention, there is provided aprobe for treating a neurodegenerative disease in a patient, comprising:

-   -   a) a proximal portion adapted to fit within a portion of a nasal        cavity and having a red light emitter,    -   b) a distal portion having a handgrip having a knurled surface        and a red light activation button, and    -   c) a red light source.

It has also been noticed by the inventors that the sphenoidal sinus ofthe nasal cavity lies adjacent important structures in the brain. Thepresent inventors believe that irradiation of this sinus structure willallow for the therapeutic transmission of red light from the sphenoidalsinus to brain structures that may be affected by Alzheimer's Disease.

Therefore, in accordance with the present invention, there is provided amethod of treating a patient having an neurodegenerative disease,comprising the step of:

-   -   a) irradiating a portion of a sphenoidal sinus with an effective        amount of red light.

Now referring to FIG. 6, the upper wall that defines the sphenoidalsinus lies just below and slightly anterior to the hypothalamus.Accordingly, directing red light from the interior of the sinus in thedirection of the upper wall will cause light to traverse that upper walland penetrate hypothalamic tissue and provide a therapeutic benefitthereto.

Therefore, in accordance with the present invention, there is provided amethod of treating a patient having a hypothalamus, comprising the stepof:

-   -   a) irradiating the hypothalamus with an effective amount of red        light.

Preferably, light is directed to the sinus by the use of a cathetercontaining a fiber optic cable, whereby the catheter can be directedunder fluoroscopy from the nasal cavity through the opening of thesphenoidal sinus and into the sinus. The fiber optic cable at theproximal end of the catheter may be connected to a red light source,while the distal end of the fiber optic is adapted to emit the redlight. In some embodiments, red light exits the distal end of thecatheter in a substantially axial fashion. Accordingly, now referring toFIG. 7, in these embodiments, the axis of the distal end portion 21 ofthe fiber optic cable 23 should be directed at the hypothalamus.

In some embodiments, the distal end of the catheter is adapted with adiffuser to diffuse the red light in a plurality of directions.Accordingly, the distal end of this catheter need not be directed at thehypothalamus in order to convey red light thereto. In some embodimentsthereof, as now referring to FIG. 8, the distal end of the fiber opticis equipped with a convex reflective surface 25 pointing in the proximaldirection. Red light entering the distal end portion of the fiber opticreflects off the reflective surface in all radial directions, therebyirradiating the desired portion of the sphenoidal sinus andhypothalamus.

Now referring to FIG. 9, in one embodiment, the catheter 23 entering thesphenoidal sinus is equipped with a dual lumen catheter having a redlight fiber optic 27 housed in a first lumen. The distal end of thesecond lumen 29 is attached to a deflated balloon having a partiallyreflective surface, while the proximal end of the second lumen isattached to a source of air. When the dual lumen catheter is insertedinto the sphenoidal sinus, the air source is activated, therebyinflating the balloon 31 to conform with the contour of the sphenoidalsinus. Thereafter, delivery of red light to the distal end of the fiberoptic has the effect of irradiating the entire surface of the balloon,thereby irradiating substantially all of the sphenoidal sinus andtherefore the hypothalamus. Now referring to FIG. 10, in someembodiments, a light transmissive pin 33 in inserted into the upper wallof the nasal cavity substantially at the junction between the cribriformplate and the anterior wall of the sphenoidal sinus. The pin is orientedto point substantially in the direction of the hypothalamus. Because thepin is light transmissive, there is substantially no absorption of theas light travels through the pin. Delivery of red light to the proximalend of the pin travels through the pin and exits the distal end of thepin. When light exits the distal end of the pin, it travels in asubstantially axial direction substantially directly at thehypothalamus.

Preferably, the pin has a glass core a threaded outer surface comprisinga light reflective material. In preferred embodiments, the pin is ametallic screw having an axial throughbore bore filled with glass or ared light transmissive polymer.

Therefore, in accordance with the present invention, there is provided amethod of treating a patient having an neurodegenerative disease,comprising the step of:

-   -   a) placing a red light transmissive pin in a bony portion of a        nasal cavity, and    -   b) directing red light through the pin.

Another brain structure intimately associated with Alzheimer's Diseaseis the amygdala. The amygdala is part of the limbic system and islocated substantially near the inner medial surface of the lower portionof the temporal lobe of the brain. It is located slightly medial to theanterior portion of the hippocampus. The amygdala plays a major role inmany important CNS functions, including control of emotions. It has beenreported that the amygdala is often one of the first structures affectedby Alzheimer's Disease, with degeneration appearing slightly afterdegeneration of the hippocampus.

Now referring to FIG. 11, it has further been noticed by the presentinventors that the amygdala AM resides substantially lateral to andslightly posterior to the sphenoidal sinus, and is separated from thesphenoidal sinus only by the thin optic nerve.

Accordingly, the present inventors believe that the sphenoidal sinus maybe used as a base for a red light emitting catheter or implant that candirect therapeutic amounts of red light to the amygdala.

In some embodiments, the preferred catheters described above forirradiating the hypothalamus may also be used to irradiate the amygdala.

Therefore, in accordance with the present invention, there is provided amethod of treating a patient having an amygdala, comprising the step of:

-   -   a) irradiating the amygdala with an effective amount of red        light.

Now referring back to FIG. 6, it has further been noticed by the presentinventors that the frontal sinus abuts a large portion of the basalprefrontal cortex. Accordingly, the present inventors believe that thefrontal sinus may be used as a base for a red light emitting catheterthat can direct therapeutic amounts of red light to the anterior portionof the basal prefrontal cortex. In some embodiments, the preferredcatheters described above for irradiating the hypothalamus may also beinserted into the frontal sinus and used to irradiate the basalprefrontal cortex.

In another embodiment, as in FIG. 12, a transmissive pin 35 ispositioned through the palantine bone located on the floor of the nasalcavity (the inferior nasal concha). In use, a red light source may beplaced in the mouth and red light is shined through the transmissivepin. Because the axis of the pin is directed to the cribriform plate,red light is shined from the mouth and through the cribriform plate tothe olfactory bulb.

Therefore, in accordance with the present invention, there is provided amethod of treating or preventing Alzheimer's disease, comprising thesteps of:

-   -   a) providing an implant having a red light source,    -   b) positioning the implant within a nasal cavity, and    -   c) activating the red light source to irradiate brain tissue        with an amount of red light.

In some embodiments, red light is provided via an implant implantedwithin the sphenoidal sinus.

In some embodiments, the implant is simply a light conduit that allowsred light to travels from the nasal cavity outside the sphenoidal sinus,through the sphenoidal sinus and into the brain. Now referring to FIG.13 a, there is provided a first exemplary red light conduit implanthaving an external red light source. Externally based-control device hasa red light source 101 for generating red light within the implanteddevice. The light generated by this source is transmitted through fiberoptic cable 103 through the patient's nasal cavity to aninternally-based light conduit 109 provided on the implant 201. In someembodiments, portions of the outer surface of the light conduit arecoated with a reflective material 111.

Now referring to FIG. 13 b, there is provided another implantembodiment, wherein the red light exits the conduit at an angle.

Now referring to FIG. 14, there is provided a second exemplary red lightunit having an internal red light source. Intransally-based energydevice 222 has an RF energy source 224 and an antenna 230 fortransmitting signals to an internally-based antenna 232 provided on theimplant 201. These antennae 230, 232 may be electro-magnetically coupledto each other. The internal antenna 232 sends electrical power through aconductor 236 situated within an insulator 238 to a red light emittingdiode (LED) 234 disposed internally within the implant in response tothe transmitted signal transmitted by the external antenna 230. The redlight generated by the LED travels through the translucent distalportion 231 of the implant, across the sphenoidal sinus and into thebrain.

In some embodiments, the telemetry portion of the device is provided byconventional, commercially-available components. For example, theexternally-based power control device can be any conventionaltransmitter, preferably capable of transmitting at least about 40milliwatts of energy to the internally-based antenna. Examples of suchcommercially available transmitters include Microstrain, Inc.Burlington, Vt. Likewise, the internally-based power antenna can be anyconventional antenna capable of producing at least about 40 milliwattsof energy in response to coupling with the externally-generated Rfsignal. Examples of such commercially available antennae include thoseused in the Microstrain Strinlink™ device. Conventionaltransmitter-receiver telemetry is capable of transmitting up to about500 milliwatts of energy to the internally-based antenna.

In some embodiments, the implant further contains an internal powersource, such as a battery (not shown), which is controlled by aninternal receiver and has sufficient energy stored therein to deliverelectrical power to the red light source of the implant in an amountsufficient to cause the desired effect.

In some embodiments, a bone screw is provided with the red light LED.Now referring to FIG. 15, in some embodiments, the bone screw 121comprises:

-   -   a) a body portion 123 made from a light transmissible material        (such as single crystal sapphire),    -   b) an outer surface 125 at least a portion of which is threaded        126,    -   c) a proximal portion 127,    -   d) a distal portion 129 containing a reflective head portion 131        having a convex reflective surface,    -   e) a red light source 135 (such as an LED) disposed upon the        proximal portion of the screw, and    -   f) an antenna 137 in electrical connection with the light        source.

In other embodiments, the red light LED and antenna are replaced with alight port, and the light source is externally based.

The present inventors believe that AD may be more effectively preventedthan treated. Prevention is more likely to be the most-cost effectiveapproach, considering the enormous cost and morbidity of AD-relatedcomplications. It would be desirable to achieve a low inflammatory, lowoxidant environment in the brain. This could be accomplished byregulating diet for high risk AD patients.

1. A method of treating a patient having a hypothalamus, comprising thestep of: a) irradiating the hypothalamus with an effective amount of redlight.